Edelfosine is a well-known compound that has been researched and studied predominately for anti-cancer treatments for many years. Edelfosine has not, however, been the subject of study to see its effects on seizures and other neurological disorders and diseases. What we have found through research and study is that edelfosine surprisingly has good results in alleviating seizures, in particular cholinergic seizures, which result from overstimulation of muscarinic receptors.
Cholinergic muscarinic overstimulation can be achieved by irreversible inhibitors of acetylcholinesterase, like chemical warfare nerve agents (CWNA) (de Araujo Furtado, M. et al., 2012), or muscarinic agonists. Pilocarpine, a muscarinic agonist, overstimulates M1 muscarinic receptors causing acute seizures followed days later by chronic seizures that emulate clinical epilepsy. It is possible that status epilepticus (SE) naturally increases brain acetylcholine and choline (Carriere, J. L. El-Fakahany, E. E., 2000, Costa, L. G. Murphy, S. D., 1984), which overstimulates M1 receptors (Jope, R. S. Gu, X., 1991). In all cases, muscarinic hyper-stimulation enhances the release of glutamate, causes seizures, excitotoxicity, astrocytes activation, neuronal death and brain injury. Interestingly the link between muscarinic hyper-stimulation and the resulting glutamate excitotoxicity was heretofore unknown. This gap of knowledge is an impediment for the development of novel therapeutic interventions targeting early steps of CWNA toxicity and yet unexplored processes leading to SE.
Based on our research and study of these mechanisms, we have found surprisingly that edelfosine can effectively prevent the effects of seizures, which may be particularly useful for subjects suffering from epilepsy or chemical nerve agent exposure. It also appears that edelfosine may be helpful for seizures relating to Alzheimer's disease, as about 20% of Alzheimer's patients develop unprovoked late onset seizures. Further, other synthetic ether alkyl-lysophospholipids (APLs) show promise in similarly reducing seizures. Such molecules include perifosine.